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Expression And Signification Of Rcas1 And Caspase-8 In Esophageal Squamous Cell Carcinoma

Posted on:2010-12-29Degree:MasterType:Thesis
Country:ChinaCandidate:X L LiFull Text:PDF
GTID:2194360302476232Subject:Pathology and pathophysiology
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Background and objectives:RCAS1(receptor-binding cancer antigen express on SiSo cells) was a novel tumor-associated antigen,a typeⅢtransmembrane protein with a Golgi-predominant localization,recognized by Sonoda,et al in the study on human cervical adenocarcinoma.RCAS1,encode 40kD and 80 kD proteins,is a kind of typeⅢtransmembrance protein,expressed in the membrance of Golgi's body.Researches found that RCAS1 might act as a ligand to induce apoptosis of tumor-infiltration lymphocytes(TILs) with its specficly receptor,this may be one of the mechanisms of evasion from immune surveillance of RCAS1 overexpression tumor cells.It was found that RCAS1 expressed in many tumor tissues as uterine tumors,ovary tumors, breast cancer,esophageal squamous cell carcinoma(ESCC),liver carcinoma,colon carcinoma,lung cancer and Hodgkin's lymphoma in recent years,whereas in normal tissue it showed negative expression.It was thought that the overexpression of RCAS1 was associated with oncogenesis,development and tumor immune escape of many kinds of human malignacies.The caspases are a family of cysteine specific proteases that are main executors of the apoptosis process.These zymogens can be cleaved to form active enzymes following the induction of apoptosis.Caspase-8,an important member of the caspase family,is a key promoter in cell apoptosis mediated by death receptor.It can autoactivate by oligomerization and self-cleavage and then activate downstream Caspase to lead apoptotic effect.Low expression of Caspase-8 is associated with oncogenesis,development and tumor immune escape of many kinds of human malignant tumors.Esophageal carcinoma is a malignant tumor that seriously affect people's health. In our country,ESCC was the most common type of esophageal carcinoma.In this research,the immunohistochemistry SP technology was performed to detect the expression of RCAS1 and Caspase-8 protein in ESCC,tumor-adjacent atypical hyperplasia tissues and normal mucosa of the esophagus;the TUNEL method was performed to analyze the apoptosis of tumor cells in ESCC tissues.This study aims to explore the relation between oncogenesis and development of ESCC and the Clinical significance.Methods1.Using the immunohistochemistry SP technology to detect the expression of RCAS1 and Caspase-8 protein in 62 cases of ESCC,34 cases of tumor-adjacent atypical hyperplasia tissues and 21 cases of normal mucosa of the esophagus respectively.The TUNEL method was performed to analyzed the apoptosis of tumor cells in ESCC tissues.2.Statistical analysis:All the data were analyzed by SPSS 12.0 statistical package, the Chi-square was used in the comparison of expression intensity of RCAS1 and Caspase-8;the relation of two variables were analyzed by the spearman level correlation analysis,the level of significant difference wasα=0.05.Analysis of variance and t test were used in the comparison of the apoptosis index(AI),P<0.05 indicated significant difference.Results1.The positive expression rates of RCAS1 protein in normal mucosa of the esophagus, tumor-adjacent atypical hyperplasia tissues and ESCC tissues increased in turn,they were 23.81%(5/21),61.76%(21/34) and 85.48%(53/62) respectively,the positive expression rates compared with each other showed stastical significance.In ESCC tissues,the quantity of RCAS1 expression was not associated with age and gender of patients and was correlated with differentiation grading,lymph node metastasis and infiltration depth of tumors.The expression rate of RCAS1 protein in carcinoma tissues without invaded out layer was lower than that with invaded out layer,the difference was statistically significant(χ~2=4.108,P=0.043);the positive expression rate in carcinoma without lymph node metastasis was lower than that with lymph node metastasis(χ~2=7.467,P=0.006);the expression rate of RCAS1 protein increased as the differentiation grading decreased(χ~2=6.179,P=0.046).2.The positive expression rates of Caspase-8 protein in normal mucosa of the esophagus,tumor-adjacent atypical hyperplasia tissues and ESCC tissues decreased in turn,they were were 80.95%(17/21),52.94%(18/34) and 32.26%(20/62) respectively,the positive expression rates compared with each other showed stastical significance(P<0.05).In ESCC tissues,the positive expression rate of Caspase-8 protein was not associated with age and gender of patients and was correlated with differentiation grading,lymph node metastasis and infiltration depth of tumors.The positive expression rate of Caspase-8 protein in carcinoma tissues without invaded out layer was higher than that with invaded out layer,the difference was statistically significant(χ~2=8.798,P=0.003);The positive expression rate of Caspase-8 protein in carcinoma without lymph node metastasis was higher than that with lymph node metastasis(χ~2=13.697,P=0.000);the expression of Caspase-8 decreased as the differentiation grading decreased(χ~2=12.405,P=0.002).3.There was correlation between expression of RCAS1 protein and apoptosis of tumor cells in ESCC.The AI of tumor cells in the group with positive expression of RCAS1 protein was(7.35±4.33)%,it was lower than that in the negative expression group(11.53±3.62)%,the difference was of statistical significance(P<0.05).4.There was correlation between expression of Caspase-8 protein and apoptosis of tumor cells in ESCC.The AI of tumor cells in the group with positive expression of RCAS1 protein was(10.53±4.33)%,it was higher than that in the negative expression group(6.75±4.99)%,the difference was of statistical significance(P<0.05).5.The relativity of RCAS1 and Caspase-8 protein in ESCC was analyzed statistically. Results showed that the two was also negatively correlated(P<0.01).Conclusions:1.The abnormal expression of RCAS1 and Caspase-8 protein were closely relative with carcinogenesis and development of ESCC,they probably played synergistic effect in carcinogenesis and development squamous carcinoma of esophagus.2.The abnormal expressions of RCAS1 and Caspase-8 were significantly correlated with infiltration depth,lymph node metastasis and differentiation grading of tumors; there was no significant correlation between the expression and age and gender of patients.It was indicated that the abnormal expression of RCAS1 and Caspase-8 correlate with the patient's prognosis in ESCC closely。...
Keywords/Search Tags:esophageal squamous cell carcinoma (ESCC), RCAS1, Caspase-8, cell apoptosis
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